Phase I/II Study of Metastatic Cancer That Expresses MAGE-A3/12 Using Lymphodepleting Conditioning Followed by Infusion of Anti-MAGE-A3/12 TCR-Gene Engineered Lymphocytes
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Toxicity Profile
研究概览
简要总结
Background:
- MAGE-A3/12 is a type of protein commonly found on certain types of cancer cells, particularly in metastatic cancer. Researchers have developed a process to take lymphocytes (white blood cells) from cancer patients, modify them in the laboratory to target cancer cells that contain MAGE-A3/12, and return them to the patient to help attack and kill the cancer cells. These modified white blood cells are an experimental treatment, but researchers are interested in determining their safety and effectiveness as a possible treatment for cancers that involve MAGE-A3/12.
Objectives:
- To evaluate the safety and effectiveness of anti-MAGE-A3/12 lymphocytes as a treatment for metastatic cancers that have not responded to standard treatment.
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with metastatic melanoma, renal cell cancer, or another type of metastatic cancer that has not responded to standard treatment.
Design:
- Participants will be screened with a full medical history and physical examination, as well as blood and urine tests, tumor samples, and imaging studies.
- Participants will have leukapheresis to collect enough white blood cells for modification in the laboratory.
- Seven days before the start of anti-MAGE-A3/12 treatment, participants will have chemotherapy with cyclophosphamide and fludarabine to suppress the immune system in preparation for the treatment.
- After the last dose of chemotherapy, participants will receive the anti-MAGE-A3/12 cells as an infusion for 20 to 30 minutes, followed by a dose of interleukin-2 to keep the anti-MAGE-A3/12 cells alive and active as long as possible. Participants will also receive filgrastim to encourage the production of blood cells.
- Participants will remain in the hospital to be monitored for possible side effects, and after release from the hospital will have regular followup exams with blood samples and imaging studies to evaluate the effectiveness of the treatment....
详细描述
Background
We have constructed a single retroviral vector that contains both alpha and beta chains of a T cell receptor (TCR) that recognizes the MAGE-A3/12 tumor antigen, which can be used to mediate genetic transfer of this TCR with high efficiency (> 30%) without the need to perform any selection.
In co-cultures with human leukocyte antigen serotype within HLA-A serotype group (HLA-A2) and MAGE-A3/12 double positive tumors, anti-MAGE-A3/12 TCR transduced T cells secreted significant amounts of Interferon (IFN)-gamma with high specificity.
Objectives:
Primary objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Ph I:Anti-MAGE A3/12 TCR PBL 5x10e9
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase I: The study will begin by evaluating the safety of two ranges of cells, 5x10^9-3x10^10, and greater than 3x10^10-1x10^11 in a standard phase I dose escalation fashion using a 3+3 design.
干预措施: PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes (Biological)
Ph I:Anti-MAGE A3/12 TCR PBL 5x10e9
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase I: The study will begin by evaluating the safety of two ranges of cells, 5x10^9-3x10^10, and greater than 3x10^10-1x10^11 in a standard phase I dose escalation fashion using a 3+3 design.
干预措施: Aldesleukin (Drug)
Ph I:Anti-MAGE A3/12 TCR PBL 5x10e9
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase I: The study will begin by evaluating the safety of two ranges of cells, 5x10^9-3x10^10, and greater than 3x10^10-1x10^11 in a standard phase I dose escalation fashion using a 3+3 design.
干预措施: Cyclophosphamide (Drug)
Ph I:Anti-MAGE A3/12 TCR PBL 5x10e9
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase I: The study will begin by evaluating the safety of two ranges of cells, 5x10^9-3x10^10, and greater than 3x10^10-1x10^11 in a standard phase I dose escalation fashion using a 3+3 design.
干预措施: Fludarabine (Drug)
Ph I:Anti-MAGE A3/12 TCR PBL 3x10e10
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase I: The study will begin by evaluating the safety of two ranges of cells, 5x10^9-3x10^10, and greater than 3x10^10-1x10^11 in a standard phase I dose escalation fashion using a 3+3 design.
干预措施: PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes (Biological)
Ph I:Anti-MAGE A3/12 TCR PBL 3x10e10
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase I: The study will begin by evaluating the safety of two ranges of cells, 5x10^9-3x10^10, and greater than 3x10^10-1x10^11 in a standard phase I dose escalation fashion using a 3+3 design.
干预措施: Aldesleukin (Drug)
Ph I:Anti-MAGE A3/12 TCR PBL 3x10e10
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase I: The study will begin by evaluating the safety of two ranges of cells, 5x10^9-3x10^10, and greater than 3x10^10-1x10^11 in a standard phase I dose escalation fashion using a 3+3 design.
干预措施: Cyclophosphamide (Drug)
Ph I:Anti-MAGE A3/12 TCR PBL 3x10e10
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase I: The study will begin by evaluating the safety of two ranges of cells, 5x10^9-3x10^10, and greater than 3x10^10-1x10^11 in a standard phase I dose escalation fashion using a 3+3 design.
干预措施: Fludarabine (Drug)
Ph II:Anti-MAGE TCR PBL MTD+HD IL-2
Phase II:Anti-MAGE A3/12 TCR PBL MTD + HD IL-2, Melanoma, RCC
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase II:patients will be entered into two cohorts based on histology:cohort 1 will include patients with metastatic melanoma or renal cell cancer; cohort 2 will include patients with other types of metastatic cancer.
干预措施: PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes (Biological)
Ph II:Anti-MAGE TCR PBL MTD+HD IL-2
Phase II:Anti-MAGE A3/12 TCR PBL MTD + HD IL-2, Melanoma, RCC
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase II:patients will be entered into two cohorts based on histology:cohort 1 will include patients with metastatic melanoma or renal cell cancer; cohort 2 will include patients with other types of metastatic cancer.
干预措施: Aldesleukin (Drug)
Ph II:Anti-MAGE TCR PBL MTD+HD IL-2
Phase II:Anti-MAGE A3/12 TCR PBL MTD + HD IL-2, Melanoma, RCC
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase II:patients will be entered into two cohorts based on histology:cohort 1 will include patients with metastatic melanoma or renal cell cancer; cohort 2 will include patients with other types of metastatic cancer.
干预措施: Cyclophosphamide (Drug)
Ph II:Anti-MAGE TCR PBL MTD+HD IL-2
Phase II:Anti-MAGE A3/12 TCR PBL MTD + HD IL-2, Melanoma, RCC
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase II:patients will be entered into two cohorts based on histology:cohort 1 will include patients with metastatic melanoma or renal cell cancer; cohort 2 will include patients with other types of metastatic cancer.
干预措施: Fludarabine (Drug)
Ph II:Anti-MAGE A3/12 TCR PBL MTD
Phase II: Anti-MAGE A3/12 TCR PBL MTD + HD-IL2 Other Cancer
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase II:patients will be entered into two cohorts based on histology:cohort 1 will include patients with metastatic melanoma or renal cell cancer; cohort 2 will include patients with other types of metastatic cancer.
干预措施: PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes (Biological)
Ph II:Anti-MAGE A3/12 TCR PBL MTD
Phase II: Anti-MAGE A3/12 TCR PBL MTD + HD-IL2 Other Cancer
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase II:patients will be entered into two cohorts based on histology:cohort 1 will include patients with metastatic melanoma or renal cell cancer; cohort 2 will include patients with other types of metastatic cancer.
干预措施: Aldesleukin (Drug)
Ph II:Anti-MAGE A3/12 TCR PBL MTD
Phase II: Anti-MAGE A3/12 TCR PBL MTD + HD-IL2 Other Cancer
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase II:patients will be entered into two cohorts based on histology:cohort 1 will include patients with metastatic melanoma or renal cell cancer; cohort 2 will include patients with other types of metastatic cancer.
干预措施: Cyclophosphamide (Drug)
Ph II:Anti-MAGE A3/12 TCR PBL MTD
Phase II: Anti-MAGE A3/12 TCR PBL MTD + HD-IL2 Other Cancer
Cyclophosphamide : 60 mg/kg/day x 2 days intravenous (IV)
Aldesleukin : 720,000 IU/kg every 8 hours for a maximum of 15 doses
PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) Transduced Autologous Peripheral Blood Lymphocytes :
Fludarabine : 25 mg/m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.
Note for phase II:patients will be entered into two cohorts based on histology:cohort 1 will include patients with metastatic melanoma or renal cell cancer; cohort 2 will include patients with other types of metastatic cancer.
干预措施: Fludarabine (Drug)
结局指标
主要结局
Toxicity Profile
时间窗: 2 years
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Clinical Tumor Regression (Complete Response (CR) + Partial Response (PR)) in Patients With Metastatic Cancer
时间窗: 2 years
Tumor regression response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is a disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
次要结局
未报告次要终点
研究者
Steven Rosenberg, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)